A novel reverse microemulsion (RM) mediated synthesis of glucose-responsive nanoparticles was developed for controlled insulin delivery. Nanoparticles were constructed using a model system comprised of dextran, poly(α-1,6 glucose), physically crosslinked with the tetrafunctional glucose-binding protein, Con A. A rapid-screening technique was used to quantify RM phase behavior in the presence of dextran, Con A and insulin. The extent of the RM existence region diminishes with increasing dextran and Con A concentrations and with increasing dextran molecular weight. Crosslinking efficiency between Con A and fluorescein isothiocyanate dextran (FITC-Dex) was found to depend on the total concentration of Con A as well as the ratio of Con A to FITC-Dex. Functionalizing dextran with higher affinity mannose ligands and increasing dextran molecular weight both improved crosslinking efficiency. The nanoparticles dissolved when dispersed in buffered saline solutions containing elevated glucose concentrations and were most responsive within the physiological range. Finally, insulin was encapsulated in select formulations and found to release preferentially at these elevated glucose concentrations. / Singapore-MIT Alliance (SMA)

Magnetic nanoparticles find broad applications in biomedical field such as drug delivery, hyperthermia and magnetic resonance imaging (MRI). For these applications magnetic nanoparticles need to be coated with suitable materials which are soluble, biocompatible and nontoxic. Among these materials, silica is the most often used coating material. This thesis is focused on preparation of silica coated iron oxide magnetic nanoparticles. Magnetic iron oxide nanoparticles are synthesized by thermal decomposition method. In the presence of iron acetylacetonate Fe(acac)3, a high boiling point organic solvent and a reducing agent, particle sizes ranging from about 5 nm to 7 nm were obtained. Nanoparticles were characterized by transmission electron microscopy (TEM). The obtained nanoparticles were coated with ultra thin silica shell via reverse microemulsion method. The influence of the amount of Igepal CO-520, NH4OH and TEOS was studied systematically and their amounts were optimized to yield monodisperse and well defined particles. The size of the silica coated magnetic nanoparticles and their agglomerates were determined by TEM images and particle size analyzer (zeta sizer). X-Ray photoelectron spectroscopy (XPS) was used to confirm the presence of silica whenever the coating could not be seen by TEM measurements. Magnetic nanoparticles having 4-6 nm thickness of silica shell were obtained. The results showed that the amount of surfactant Igepal CO-520 played an important role in the reaction system.